Skip to main content
SpringerLink
Log in
Book cover

Reviews of Physiology, Biochemistry and Pharmacology, Vol. 165 pp 1–30Cite as

The Exocrine Pancreas: The Acinar-Ductal Tango in Physiology and Pathophysiology

  • Chapter
  • First Online:

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 165))

Abstract

There are many reviews of pancreatic acinar cell function and also of pancreatic duct function, but there is an almost total absence of synthetic reviews bringing the integrated functions of these two vitally and mutually interdependent cells together. This is what we have attempted to do in this chapter. In the first part, we review the normal integrated function of the acinar-ductal system, with particular emphasis on how regulation of one type of cell also influences the other cell type. In the second part, we review a range of pathological processes, particularly those involved in acute pancreatitis (AP), an often-fatal human disease in which the pancreas digests itself, in order to explore how malfunction of one of the cell types adversely affects the function of the other.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ACh:

Acetylcholine

ASICs:

Acid-sensing ion channels

AP:

Acute pancreatitis

ATP:

Adenosine-5′-triphosphate

UTP:

Alpha-d-glucose-1-phosphate uridylyltransferase

CLCs:

Ca2+-activated Cl− channels

CaM:

Calmodulin

PRSS1:

Cationic trypsinogen

CCK:

Cholecystokinin

CTRC:

Chymotrypsin C

cAMP:

Cyclic adenosine monophosphate

cGMP:

Cyclic guanosine monophosphate

CF:

Cystic fibrosis

DIDS:

Diisothiocyanostilbene disulfonate

FAEEs:

Fatty acid ethyl esters

FAs:

Fatty acids

IP3 :

Inositol triphosphate

[Ca2+]i :

Intracellular Ca2+ level

IRK-8:

Inwardly rectifying K+ -8

P2X:

Ionotropic purinoceptor

NHE:

Na+/H+ exchangers

PSTI:

Pancreatic secretory trypsin inhibitor

PMCA:

Plasma membrane Ca2+ ATPase pump

KCNQ1:

Potassium voltage-gated channel subfamily Q, member 1

PAR2:

Protease-activated receptor 2

ROS:

Reactive oxygen species

SERCA:

Sarco/endoplasmic reticulum Ca2+-ATPase

TLC:

Taurolithocholic acid

TRPVs:

Transient receptor potential ion channels of the vanilloid subtype

KCNKs:

Two-pore domain potassium channels

TWIK-2:

Two-pore domain weakly inward rectifying

ZGs:

Zymogen granules

References

  • Alexandre M, Pandol SJ, Gorelick FS, Thrower EC (2011) The emerging role of smoking in the development of pancreatitis. Pancreatology 11:469–474

    PubMed  CAS  Google Scholar 

  • Allen-Mersh TG (1985) What is the significance of pancreatic ductal mucinous hyperplasia? Gut 26:825–833

    PubMed  CAS  Google Scholar 

  • Aponte GW, Park K, Hess R, Garcia R, Taylor IL (1989) Meal-induced peptide tyrosine tyrosine inhibition of pancreatic secretion in the rat. FASEB J 3:1949–1955

    PubMed  CAS  Google Scholar 

  • Apte MV, Norton ID, Wilson JS (1994) Ethanol induced acinar cell injury. Alcohol Alcohol Suppl 2:365–368

    PubMed  CAS  Google Scholar 

  • Apte MV, Wilson JS, McCaughan GW, Korsten MA, Haber PS, Norton ID, Pirola RC (1995) Ethanol-induced alterations in messenger RNA levels correlate with glandular content of pancreatic enzymes. J Lab Clin Med 125:634–640

    PubMed  CAS  Google Scholar 

  • Apte MV, Pirola RC, Wilson JS (2010) Mechanisms of alcoholic pancreatitis. J Gastroenterol Hepatol 25:1816–1826

    PubMed  CAS  Google Scholar 

  • Argent BE (2006) Cell physiology of pancreatic ducts. In: Johnson LR (ed) Physiology of the gastrointestinal tract, vol 2. Elsevier, San Diego, pp 1376–1396

    Google Scholar 

  • Armstrong CP, Taylor TV, Torrance HB (1985) Effects of bile, infection and pressure on pancreatic duct integrity. Br J Surg 72:792–795

    PubMed  CAS  Google Scholar 

  • Awla D, Abdulla A, Regner S, Thorlacius H (2011) TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate. Inflamm Res 60:1093–1098

    PubMed  CAS  Google Scholar 

  • Barrow SL, Voronina SG, da Silva Xavier G, Chvanov MA, Longbottom RE, Gerasimenko OV, Petersen OH, Rutter GA, Tepikin AV (2008) ATP depletion inhibits Ca2+ release, influx and extrusion in pancreatic acinar cells but not pathological Ca2+ responses induced by bile. Pflugers Arch 455:1025–1039

    PubMed  CAS  Google Scholar 

  • Behrendorff N, Floetenmeyer M, Schwiening C, Thorn P (2010). Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice. Gastroenterology 139:1711–1720, 1720 e1711–1715

    Google Scholar 

  • Bhoomagoud M, Jung T, Atladottir J, Kolodecik TR, Shugrue C, Chaudhuri A, Thrower EC, Gorelick FS (2009) Reducing extracellular pH sensitizes the acinar cell to secretagogue-induced pancreatitis responses in rats. Gastroenterology 137:1083–1092

    PubMed  CAS  Google Scholar 

  • Booth DM, Murphy JA, Mukherjee R, Awais M, Neoptolemos JP, Gerasimenko OV, Tepikin AV, Petersen OH, Sutton R, Criddle DN (2011) Reactive oxygen species induced by bile acid induce apoptosis and protect against necrosis in pancreatic acinar cells. Gastroenterology 140:2116–2125

    PubMed  CAS  Google Scholar 

  • Braganza JM, Rao JJ (1978) Disproportionate reduction in tryptic response to endogenous compared with exogenous stimulation in chronic pancreatitis. Br Med J 2:392–394

    PubMed  CAS  Google Scholar 

  • Braun M, Thevenod F (2000) Photoaffinity labeling and purification of ZG-16p, a high-affinity dihydropyridine binding protein of rat pancreatic zymogen granule membranes that regulates a K(+)-selective conductance. Mol Pharmacol 57:308–316

    PubMed  CAS  Google Scholar 

  • Bruce JI, Yang X, Ferguson CJ, Elliott AC, Steward MC, Case RM, Riccardi D (1999) Molecular and functional identification of a Ca2+ (polyvalent cation)-sensing receptor in rat pancreas. J Biol Chem 274:20561–20568

    PubMed  CAS  Google Scholar 

  • Chen X, Andrews PC (2008) Purification and proteomics analysis of pancreatic zymogen granule membranes. Methods Mol Biol 432:275–287

    PubMed  CAS  Google Scholar 

  • Chen X, Andrews PC (2009) Quantitative proteomics analysis of pancreatic zymogen granule membrane proteins. Methods Mol Biol 528:327–338

    PubMed  CAS  Google Scholar 

  • Chen EY, Yang N, Quinton PM, Chin WC (2010) A new role for bicarbonate in mucus formation. Am J Physiol Lung Cell Mol Physiol 299:L542–L549

    PubMed  CAS  Google Scholar 

  • Cosen-Binker LI, Lam PP, Binker MG, Reeve J, Pandol S, Gaisano HY (2007) Alcohol/cholecystokinin-evoked pancreatic acinar basolateral exocytosis is mediated by protein kinase C alpha phosphorylation of Munc18c. J Biol Chem 282:13047–13058

    PubMed  CAS  Google Scholar 

  • Cosen-Binker LI, Binker MG, Wang CC, Hong W, Gaisano HY (2008) VAMP8 is the v-SNARE that mediates basolateral exocytosis in a mouse model of alcoholic pancreatitis. J Clin Invest 118:2535–2551

    PubMed  CAS  Google Scholar 

  • Criddle DN, Raraty MG, Neoptolemos JP, Tepikin AV, Petersen OH, Sutton R (2004) Ethanol toxicity in pancreatic acinar cells: mediation by nonoxidative fatty acid metabolites. Proc Natl Acad Sci USA 101:10738–10743

    PubMed  CAS  Google Scholar 

  • Criddle DN, Murphy J, Fistetto G, Barrow S, Tepikin AV, Neoptolemos JP, Sutton R, Petersen OH (2006) Fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis. Gastroenterology 130:781–793

    PubMed  CAS  Google Scholar 

  • Doege H, Stahl A (2006) Protein-mediated fatty acid uptake: novel insights from in vivo models. Physiology (Bethesda) 21:259–268

    CAS  Google Scholar 

  • Dolai S, Liang T, Lam PP, Fernandez NA, Chidambaram S, Gaisano HY (2012) Effects of ethanol metabolites on exocytosis of pancreatic acinar cells in rats. Gastroenterology 143(832–843):e831–e837

    Google Scholar 

  • Farmer RC, Tweedie J, Maslin S, Reber HA, Adler G, Kern H (1984) Effects of bile salts on permeability and morphology of main pancreatic duct in cats. Dig Dis Sci 29:740–751

    PubMed  CAS  Google Scholar 

  • Ferdek PE, Gerasimenko JV, Peng S, Tepikin AV, Petersen OH, Gerasimenko OV (2012) A novel role for Bcl-2 in regulation of cellular calcium extrusion. Curr Biol 22:1241–1246

    PubMed  CAS  Google Scholar 

  • Findlay I, Petersen OH (1983) The extent of dye-coupling between exocrine acinar cells of the mouse pancreas. The dye-coupled acinar unit. Cell Tissue Res 232:121–127

    PubMed  CAS  Google Scholar 

  • Freedman SD (1998) New concepts in understanding the pathophysiology of chronic pancreatitis. Int J Pancreatol 24:1–8

    PubMed  CAS  Google Scholar 

  • Freedman SD, Kern HF, Scheele GA (1994) Apical membrane trafficking during regulated pancreatic exocrine secretion – role of alkaline pH in the acinar lumen and enzymatic cleavage of GP2, a GPI-linked protein. Eur J Cell Biol 65:354–365

    PubMed  CAS  Google Scholar 

  • Freedman SD, Kern HF, Scheele GA (1998a) Acinar lumen pH regulates endocytosis, but not exocytosis, at the apical plasma membrane of pancreatic acinar cells. Eur J Cell Biol 75:153–162

    PubMed  CAS  Google Scholar 

  • Freedman SD, Kern HF, Scheele GA (1998b) Cleavage of GPI-anchored proteins from the plasma membrane activates apical endocytosis in pancreatic acinar cells. Eur J Cell Biol 75:163–173

    PubMed  CAS  Google Scholar 

  • Freedman SD, Kern HF, Scheele GA (2001) Pancreatic acinar cell dysfunction in CFTR(−/−) mice is associated with impairments in luminal pH and endocytosis. Gastroenterology 121:950–957

    PubMed  CAS  Google Scholar 

  • Gasser KW, DiDomenico J, Hopfer U (1988) Secretagogues activate chloride transport pathways in pancreatic zymogen granules. Am J Physiol 254:G93–G99

    PubMed  CAS  Google Scholar 

  • Gerasimenko JV, Flowerdew SE, Voronina SG, Sukhomlin TK, Tepikin AV, Petersen OH, Gerasimenko OV (2006) Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors. J Biol Chem 281:40154–40163

    PubMed  CAS  Google Scholar 

  • Gerasimenko JV, Lur G, Sherwood MW, Ebisui E, Tepikin AV, Mikoshiba K, Gerasimenko OV, Petersen OH (2009) Pancreatic protease activation by alcohol metabolite depends on Ca2+ release via acid store IP3 receptors. Proc Natl Acad Sci USA 106:10758–10763

    PubMed  CAS  Google Scholar 

  • Gerasimenko JV, Lur G, Ferdek P, Sherwood MW, Ebisui E, Tepikin AV, Mikoshiba K, Petersen OH, Gerasimenko OV (2011) Calmodulin protects against alcohol-induced pancreatic trypsinogen activation elicited via Ca2+ release through IP3 receptors. Proc Natl Acad Sci USA 108:5873–5878

    PubMed  CAS  Google Scholar 

  • Goebell H, Baltzer G, Schlott KA, Bode C (1973) Parallel secretion of calcium and enzymes by the human pancreas. Digestion 8:336–346

    PubMed  CAS  Google Scholar 

  • Gorelick FS (2003) Alcohol and zymogen activation in the pancreatic acinar cell. Pancreas 27:305–310

    PubMed  CAS  Google Scholar 

  • Gullo L, Priori P, Costa PL, Mattioli G, Labo G (1984) Action of secretin on pancreatic enzyme secretion in man. Studies on pure pancreatic juice. Gut 25:867–873

    PubMed  CAS  Google Scholar 

  • Haanes KA, Novak I (2010) ATP storage and uptake by isolated pancreatic zymogen granules. Biochem J 429:303–311

    PubMed  CAS  Google Scholar 

  • Haber PS, Wilson JS, Apte MV, Pirola RC (1993) Fatty acid ethyl esters increase rat pancreatic lysosomal fragility. J Lab Clin Med 121:759–764

    PubMed  CAS  Google Scholar 

  • Haber PS, Wilson JS, Apte MV, Korsten MA, Pirola RC (1994) Chronic ethanol consumption increases the fragility of rat pancreatic zymogen granules. Gut 35:1474–1478

    PubMed  CAS  Google Scholar 

  • Hegyi P, Rakonczay Z Jr (2007) The inhibitory pathways of pancreatic ductal bicarbonate secretion. Int J Biochem Cell Biol 39:25–30

    PubMed  CAS  Google Scholar 

  • Hegyi P, Rakonczay Z (2010) Insufficiency of electrolyte and fluid secretion by pancreatic ductal cells leads to increased patient risk for pancreatitis. Am J Gastroenterol 105:2119–2120

    PubMed  Google Scholar 

  • Hegyi P, Gray MA, Argent BE (2003) Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger. Am J Physiol Cell Physiol 285:C268–C276

    PubMed  CAS  Google Scholar 

  • Hegyi P, Ordog B, Rakonczai Z Jr, Takacs T, Lonovics J, Szabolcs A, Sari R, Toth A, Papp JG, Varro A, Kovacs MK, Gray MA, Argent BE, Boldogkoi Z (2005a) Effect of herpesvirus infection on pancreatic duct cell secretion. World J Gastroenterol 11:5997–6002

    PubMed  CAS  Google Scholar 

  • Hegyi P, Rakonczay Z Jr, Tiszlavicz L, Varro A, Toth A, Racz G, Varga G, Gray MA, Argent BE (2005b) Protein kinase C mediates the inhibitory effect of substance P on HCO3 – secretion from guinea pig pancreatic ducts. Am J Physiol Cell Physiol 288:C1030–C1041

    PubMed  CAS  Google Scholar 

  • Hegyi P, Maleth J, Venglovecz V, Rakonczay Z Jr (2011a) Pancreatic ductal bicarbonate secretion: challenge of the acinar acid load. Front Physiol 2:36

    PubMed  Google Scholar 

  • Hegyi P, Pandol S, Venglovecz V, Rakonczay Z Jr (2011b) The acinar-ductal tango in the pathogenesis of acute pancreatitis. Gut 60:544–552

    PubMed  Google Scholar 

  • Hegyi P, Rakonczay Z, Venglovecz V, Wittmann T, Maleth J (2012) Non-oxidative ethanol metabolites induce intracellular ATP depletion and inhibit pancreatic ductal bicarbonate secretion in human pancreatic ductal epithelial cell line. Gastroenterology 142:S460–S460

    Google Scholar 

  • Henriksen KL, Novak I (2003) Effect of ATP on intracellular pH in pancreatic ducts involves P2X7 receptors. Cell Physiol Biochem 13:93–102

    PubMed  CAS  Google Scholar 

  • Hirota M, Shimosegawa T, Masamune A, Kikuta K, Kume K, Hamada S, Kihara Y, Satoh A, Kimura K, Tsuji I, Kuriyama S (2012) The sixth nationwide epidemiological survey of chronic pancreatitis in Japan. Pancreatology 12:79–84

    PubMed  Google Scholar 

  • Holzer P (2003) Acid-sensitive ion channels in gastrointestinal function. Curr Opin Pharmacol 3:618–625

    PubMed  CAS  Google Scholar 

  • Holzer P (2007) Taste receptors in the gastrointestinal tract. V. Acid sensing in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 292:G699–G705

    PubMed  CAS  Google Scholar 

  • Ignath I, Hegyi P, Venglovecz V, Szekely CA, Carr G, Hasegawa M, Inoue M, Takacs T, Argent BE, Gray MA, Rakonczay Z Jr (2009) CFTR expression but not Cl− transport is involved in the stimulatory effect of bile acids on apical Cl−/HCO3 – exchange activity in human pancreatic duct cells. Pancreas 38:921–929

    PubMed  CAS  Google Scholar 

  • Ishiguro H, Naruse S, Kitagawa M, Hayakawa T, Case RM, Steward MC (1999) Luminal ATP stimulates fluid and HCO3 – secretion in guinea-pig pancreatic duct. J Physiol 519(Pt 2):551–558

    PubMed  CAS  Google Scholar 

  • Iwatsuki N, Petersen OH (1978) Electrical coupling and uncoupling of exocrine acinar cells. J Cell Biol 79:533–545

    PubMed  CAS  Google Scholar 

  • Iwatsuki N, Petersen OH (1979) Direct visualization of cell to cell coupling: transfer of fluorescent probes in living mammalian pancreatic acini. Pflugers Arch 380:277–281

    PubMed  CAS  Google Scholar 

  • Iwatsuki N, Petersen OH (1981) Dissociation between stimulant-evoked acinar membrane resistance change and amylase secretion in the mouse parotid gland. J Physiol 314:79–84

    PubMed  CAS  Google Scholar 

  • Kazal LA, Spicer DS, Brahinsky RA (1948) Isolation of a crystalline trypsin inhibitor-anticoagulant protein from pancreas. J Am Chem Soc 70:3034–3040

    PubMed  CAS  Google Scholar 

  • Keller PJ, Allan BJ (1967) The protein composition of human pancreatic juice. J Biol Chem 242:281–287

    PubMed  CAS  Google Scholar 

  • Kelly ML, Abu-Hamdah R, Jeremic A, Cho SJ, Ilie AE, Jena BP (2005) Patch clamped single pancreatic zymogen granules: direct measurements of ion channel activities at the granule membrane. Pancreatology 5:443–449

    PubMed  CAS  Google Scholar 

  • Kemeny LV, Hegyi P, Rakonczay Z Jr, Borka K, Korompay A, Gray MA, Argent BE, Venglovecz V (2011) Substance P inhibits pancreatic ductal bicarbonate secretion via neurokinin receptors 2 and 3 in the guinea pig exocrine pancreas. Pancreas 40:793–795

    PubMed  Google Scholar 

  • Kim JY, Kim KH, Lee JA, Namkung W, Sun AQ, Ananthanarayanan M, Suchy FJ, Shin DM, Muallem S, Lee MG (2002) Transporter-mediated bile acid uptake causes Ca2+−dependent cell death in rat pancreatic acinar cells. Gastroenterology 122:1941–1953

    PubMed  CAS  Google Scholar 

  • Ko SB, Mizuno N, Yatabe Y, Yoshikawa T, Ishiguro H, Yamamoto A, Azuma S, Naruse S, Yamao K, Muallem S, Goto H (2010) Corticosteroids correct aberrant CFTR localization in the duct and regenerate acinar cells in autoimmune pancreatitis. Gastroenterology 138:1988–1996

    PubMed  CAS  Google Scholar 

  • Ko SB, Azuma S, Yoshikawa T, Yamamoto A, Kyokane K, Ko MS, Ishiguro H (2012) Molecular mechanisms of pancreatic stone formation in chronic pancreatitis. Front Physiol 3:415

    PubMed  Google Scholar 

  • Kordas KS, Sperlagh B, Tihanyi T, Topa L, Steward MC, Varga G, Kittel A (2004) ATP and ATPase secretion by exocrine pancreas in rat, guinea pig, and human. Pancreas 29:53–60

    PubMed  CAS  Google Scholar 

  • Kubisch CH, Logsdon CD (2008) Endoplasmic reticulum stress and the pancreatic acinar cell. Expert Rev Gastroenterol Hepatol 2:249–260

    PubMed  Google Scholar 

  • Kulaksiz H, Cetin Y (2001) Uroguanylin and guanylate cyclase C in the human pancreas: expression and mutuality of ligand/receptor localization as indicators of intercellular paracrine signaling pathways. J Endocrinol 170:267–275

    PubMed  CAS  Google Scholar 

  • Kulaksiz H, Schmid A, Honscheid M, Eissele R, Klempnauer J, Cetin Y (2001) Guanylin in the human pancreas: a novel luminocrine regulatory pathway of electrolyte secretion via cGMP and CFTR in the ductal system. Histochem Cell Biol 115:131–145

    PubMed  CAS  Google Scholar 

  • Lam KY, Leung PS (2002) Regulation and expression of a renin-angiotensin system in human pancreas and pancreatic endocrine tumours. Eur J Endocrinol 146:567–572

    PubMed  CAS  Google Scholar 

  • Lam PP, Cosen Binker LI, Lugea A, Pandol SJ, Gaisano HY (2007) Alcohol redirects CCK-mediated apical exocytosis to the acinar basolateral membrane in alcoholic pancreatitis. Traffic 8:605–617

    PubMed  CAS  Google Scholar 

  • Laposata EA, Lange LG (1986) Presence of nonoxidative ethanol metabolism in human organs commonly damaged by ethanol abuse. Science 231:497–499

    PubMed  CAS  Google Scholar 

  • Lee M, Muallem S (2008) Physiology of duct cell secretion. In: HB (ed) The pancreas. Blackwell, Massachusetts, pp 78–91

    Google Scholar 

  • Lee MG, Ahn W, Choi JY, Luo X, Seo JT, Schultheis PJ, Shull GE, Kim KH, Muallem S (2000) Na(+)-dependent transporters mediate HCO(3)(−) salvage across the luminal membrane of the main pancreatic duct. J Clin Invest 105:1651–1658

    PubMed  CAS  Google Scholar 

  • Lee WK, Torchalski B, Roussa E, Thevenod F (2008) Evidence for KCNQ1 K+ channel expression in rat zymogen granule membranes and involvement in cholecystokinin-induced pancreatic acinar secretion. Am J Physiol Cell Physiol 294:C879–C892

    PubMed  CAS  Google Scholar 

  • Leung PS (2007) The physiology of a local renin-angiotensin system in the pancreas. J Physiol 580:31–37

    PubMed  CAS  Google Scholar 

  • Leung PS, Chan HC, Fu LX, Wong PY (1997) Localization of angiotensin II receptor subtypes AT1 and AT2 in the pancreas of rodents. J Endocrinol 153:269–274

    PubMed  CAS  Google Scholar 

  • Leung PS, Chan WP, Wong TP, Sernia C (1999) Expression and localization of the renin-angiotensin system in the rat pancreas. J Endocrinol 160:13–19

    PubMed  CAS  Google Scholar 

  • Li Z, Lu M, Chu J, Qiao X, Meng X, Sun B, Zhang W, Xue D (2012) Early proteome analysis of rat pancreatic acinar AR42J cells treated with taurolithocholic acid 3-sulfate. Pancreatology 12:248–256

    PubMed  CAS  Google Scholar 

  • Liddle RA (2007) The role of transient receptor potential vanilloid 1 (TRPV1) channels in pancreatitis. Biochim Biophys Acta 1772:869–878

    PubMed  CAS  Google Scholar 

  • Lugea A, Tischler D, Nguyen J, Gong J, Gukovsky I, French SW, Gorelick FS, Pandol SJ (2010) Adaptive unfolded protein response attenuates alcohol-induced pancreatic damage. Gastroenterology 140:987–997

    PubMed  Google Scholar 

  • Luo X, Zheng W, Yan M, Lee MG, Muallem S (1999) Multiple functional P2X and P2Y receptors in the luminal and basolateral membranes of pancreatic duct cells. Am J Physiol 277:C205–C215

    PubMed  CAS  Google Scholar 

  • Luo X, Choi JY, Ko SB, Pushkin A, Kurtz I, Ahn W, Lee MG, Muallem S (2001) HCO3 – salvage mechanisms in the submandibular gland acinar and duct cells. J Biol Chem 276:9808–9816

    PubMed  CAS  Google Scholar 

  • Lur G, Haynes LP, Prior IA, Gerasimenko OV, Feske S, Petersen OH, Burgoyne RD, Tepikin AV (2009) Ribosome-free terminals of rough ER allow formation of STIM1 puncta and segregation of STIM1 from IP(3) receptors. Curr Biol 19:1648–1653

    PubMed  CAS  Google Scholar 

  • Maleth J, Venglovecz V, Razga Z, Tiszlavicz L, Rakonczay Z Jr, Hegyi P (2011) Non-conjugated chenodeoxycholate induces severe mitochondrial damage and inhibits bicarbonate transport in pancreatic duct cells. Gut 60:136–138

    PubMed  CAS  Google Scholar 

  • Maleth J, Rakonczay Z Jr, Venglovecz V, Dolman NJ, Hegyi P (2013) Central role of mitochondrial injury in the pathogenesis of acute pancreatitis. Acta Physiol (Oxf) 207(2):226–235

    Google Scholar 

  • Marteau C, Silviani V, Ducroc R, Crotte C, Gerolami A (1995) Evidence for apical Na+/H+ exchanger in bovine main pancreatic duct. Dig Dis Sci 40:2336–2340

    PubMed  CAS  Google Scholar 

  • Meda P, Findlay I, Kolod E, Orci L, Petersen OH (1983) Short and reversible uncoupling evokes little change in the gap junctions of pancreatic acinar cells. J Ultrastruct Res 83:69–84

    PubMed  CAS  Google Scholar 

  • Muili KA, Wang D, Orabi AI, Sarwar S, Luo Y, Javed TA, Eisses JF, Mahmood SM, Jin S, Singh VP, Ananthanaravanan M, Perides G, Williams JA, Molkentin JD, Husain SZ (2013) Bile acids induce pancreatic acinar cell injury and pancreatitis by activating calcineurin. J Biol Chem 288(1):570–580

    Google Scholar 

  • Mukherjee R, Criddle DN, Gukovskaya A, Pandol S, Petersen OH, Sutton R (2008) Mitochondrial injury in pancreatitis. Cell Calcium 44:14–23

    PubMed  CAS  Google Scholar 

  • Murphy JA, Criddle DN, Sherwood M, Chvanov M, Mukherjee R, McLaughlin E, Booth D, Gerasimenko JV, Raraty MG, Ghaneh P, Neoptolemos JP, Gerasimenko OV, Tepikin AV, Green GM, Reeve JR Jr, Petersen OH, Sutton R (2008) Direct activation of cytosolic Ca2+ signaling and enzyme secretion by cholecystokinin in human pancreatic acinar cells. Gastroenterology 135:632–641

    PubMed  CAS  Google Scholar 

  • Noble MD, Romac J, Vigna SR, Liddle RA (2008) A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis. Gut 57:1566–1571

    PubMed  CAS  Google Scholar 

  • Novak I (2008) Purinergic receptors in the endocrine and exocrine pancreas. Purinergic Signal 4:237–253

    PubMed  CAS  Google Scholar 

  • Opie EL (1901) The etiology of acute hemorrhagic pancreatitis. Johns Hopkins Hosp Bull 12:182–188

    Google Scholar 

  • Owyang C, MJ D (2009) Chronic pancreatitis. In: Yamada T (ed) Textbook of gastroenterology, vol 2. Wiley-Blackwell, Oxford, pp 1811–1853

    Google Scholar 

  • Page AJ, Brierley SM, Martin CM, Price MP, Symonds E, Butler R, Wemmie JA, Blackshaw LA (2005) Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function. Gut 54:1408–1415

    PubMed  CAS  Google Scholar 

  • Pallagi P, Venglovecz V, Rakonczay Z, Jr, Borka K, Korompay A, Ozsvari B, Judak L, Sahin-Toth M, Geisz A, Schnur A, Maleth J, Takacs T, Gray MA, Argent BE, Mayerle J, Lerch MM, Wittmann T, Hegyi P (2011) Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl(−) channels and luminal anion exchangers. Gastroenterology 141:2228–2239 e2226

    Google Scholar 

  • Pandol SJ, Periskic S, Gukovsky I, Zaninovic V, Jung Y, Zong Y, Solomon TE, Gukovskaya AS, Tsukamoto H (1999) Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide. Gastroenterology 117:706–716

    PubMed  CAS  Google Scholar 

  • Pandol SJ, Gorelick FS, Gerloff A, Lugea A (2010) Alcohol abuse, endoplasmic reticulum stress and pancreatitis. Dig Dis 28:776–782

    PubMed  Google Scholar 

  • Pandol SJ, Lugea A, Mareninova OA, Smoot D, Gorelick FS, Gukovskaya AS, Gukovsky I (2011) Investigating the pathobiology of alcoholic pancreatitis. Alcohol Clin Exp Res 35:830–837

    PubMed  Google Scholar 

  • Parekh AB, Putney JW Jr (2005) Store-operated calcium channels. Physiol Rev 85:757–810

    PubMed  CAS  Google Scholar 

  • Park MK, Lomax RB, Tepikin AV, Petersen OH (2001) Local uncaging of caged Ca(2+) reveals distribution of Ca(2+)-activated Cl(−) channels in pancreatic acinar cells. Proc Natl Acad Sci USA 98:10948–10953

    PubMed  CAS  Google Scholar 

  • Park M, Ko SB, Choi JY, Muallem G, Thomas PJ, Pushkin A, Lee MS, Kim JY, Lee MG, Muallem S, Kurtz I (2002) The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3 – salvage transporter human Na+−HCO3 – cotransport isoform 3. J Biol Chem 277:50503–50509

    PubMed  CAS  Google Scholar 

  • Park HW, Nam JH, Kim JY, Namkung W, Yoon JS, Lee JS, Kim KS, Venglovecz V, Gray MA, Kim KH, Lee MG (2010) Dynamic regulation of CFTR bicarbonate permeability by [Cl−]i and its role in pancreatic bicarbonate secretion. Gastroenterology 139:620–631

    PubMed  CAS  Google Scholar 

  • Patel AG, Reber PU, Toyama MT, Ashley SW, Reber HA (1999) Effect of pancreaticojejunostomy on fibrosis, pancreatic blood flow, and interstitial pH in chronic pancreatitis: a feline model. Ann Surg 230:672–679

    PubMed  CAS  Google Scholar 

  • Pazoles CJ, Pollard HB (1978) Evidence for stimulation of anion transport in ATP-evoked transmitter release from isolated secretory vesicles. J Biol Chem 253:3962–3969

    PubMed  CAS  Google Scholar 

  • Peery AF, Dellon ES, Lund J, Crockett SD, McGowan CE, Bulsiewicz WJ, Gangarosa LM, Thiny MT, Stizenberg K, Morgan DR, Ringel Y, Kim HP, Dibonaventura MD, Carroll CF, Allen JK, Cook SF, Sandler RS, Kappelman MD, Shaheen NJ (2012) Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 143(1179–1187):e1171–e1173

    Google Scholar 

  • Perides G, Laukkarinen JM, Vassileva G, Steer ML (2010) Biliary acute pancreatitis in mice is mediated by the G-protein-coupled cell surface bile acid receptor Gpbar1. Gastroenterology 138:715–725

    PubMed  CAS  Google Scholar 

  • Petersen OH (1992) Stimulus-secretion coupling: cytoplasmic calcium signals and the control of ion channels in exocrine acinar cells. J Physiol 448:1–51

    PubMed  CAS  Google Scholar 

  • Petersen OH (2005) Ca2+ signalling and Ca2+−activated ion channels in exocrine acinar cells. Cell Calcium 38:171–200

    PubMed  CAS  Google Scholar 

  • Petersen OH (2008) Physiology of acinar cell secretion. In: Beger H (ed) The pancreas. Blackwell, San Diego, pp 71–78

    Google Scholar 

  • Petersen OH, Findlay I (1987) Electrophysiology of the pancreas. Physiol Rev 67:1054–1116

    PubMed  CAS  Google Scholar 

  • Petersen OH, Maruyama Y (1984) Calcium-activated potassium channels and their role in secretion. Nature 307:693–696

    PubMed  CAS  Google Scholar 

  • Petersen OH, Sutton R (2006) Ca2+ signalling and pancreatitis: effects of alcohol, bile and coffee. Trends Pharmacol Sci 27:113–120

    PubMed  CAS  Google Scholar 

  • Petersen OH, Tepikin AV (2008) Polarized calcium signaling in exocrine gland cells. Annu Rev Physiol 70:273–299

    PubMed  CAS  Google Scholar 

  • Petersen OH, Findlay I, Iwatsuki N, Singh J, Gallacher DV, Fuller CM, Pearson GT, Dunne MJ, Morris AP (1985) Human pancreatic acinar cells: studies of stimulus-secretion coupling. Gastroenterology 89:109–117

    PubMed  CAS  Google Scholar 

  • Petersen OH, Tepikin AV, Gerasimenko JV, Gerasimenko OV, Sutton R, Criddle DN (2009) Fatty acids, alcohol and fatty acid ethyl esters: toxic Ca2+ signal generation and pancreatitis. Cell Calcium 45:634–642

    PubMed  CAS  Google Scholar 

  • Petersen OH, Gerasimenko OV, Gerasimenko JV (2011a) Pathobiology of acute pancreatitis: focus on intracellular calcium and calmodulin. F1000 Med Rep 3:15

    PubMed  Google Scholar 

  • Petersen OH, Gerasimenko OV, Tepikin AV, Gerasimenko JV (2011b) Aberrant Ca(2+) signalling through acidic calcium stores in pancreatic acinar cells. Cell Calcium 50:193–199

    PubMed  CAS  Google Scholar 

  • Quinton PM (2001) The neglected ion: HCO3. Nat Med 7:292–293

    PubMed  CAS  Google Scholar 

  • Racz GZ, Kittel A, Riccardi D, Case RM, Elliott AC, Varga G (2002) Extracellular calcium sensing receptor in human pancreatic cells. Gut 51:705–711

    PubMed  CAS  Google Scholar 

  • Rakonczay Z Jr, Fearn A, Hegyi P, Boros I, Gray MA, Argent BE (2006) Characterization of H+ and HCO3 – transporters in CFPAC-1 human pancreatic duct cells. World J Gastroenterol 12:885–895

    PubMed  CAS  Google Scholar 

  • Raraty M, Ward J, Erdemli G, Vaillant C, Neoptolemos JP, Sutton R, Petersen OH (2000) Calcium-dependent enzyme activation and vacuole formation in the apical granular region of pancreatic acinar cells. Proc Natl Acad Sci USA 97:13126–13131

    PubMed  CAS  Google Scholar 

  • Reber HA, Mosley JG (1980) The effect of bile salts on the pancreatic duct mucosal barrier. Br J Surg 67:59–62

    PubMed  CAS  Google Scholar 

  • Reber HA, Roberts C, Way LW (1979) The pancreatic duct mucosal barrier. Am J Surg 137:128–134

    PubMed  CAS  Google Scholar 

  • Regoli M, Bendayan M, Fonzi L, Sernia C, Bertelli E (2003) Angiotensinogen localization and secretion in the rat pancreas. J Endocrinol 179:81–89

    PubMed  CAS  Google Scholar 

  • Rinderknecht H (1993) Pancreatic secretory enzymes. Raven, New York

    Google Scholar 

  • Rindler MJ, Xu CF, Gumper I, Smith NN, Neubert TA (2007) Proteomic analysis of pancreatic zymogen granules: identification of new granule proteins. J Proteome Res 6:2978–2992

    PubMed  CAS  Google Scholar 

  • Rosendahl J, Witt H, Szmola R, Bhatia E, Ozsvari B, Landt O, Schulz HU, Gress TM, Pfutzer R, Lohr M, Kovacs P, Bluher M, Stumvoll M, Choudhuri G, Hegyi P, te Morsche RH, Drenth JP, Truninger K, Macek M Jr, Puhl G, Witt U, Schmidt H, Buning C, Ockenga J, Kage A, Groneberg DA, Nickel R, Berg T, Wiedenmann B, Bodeker H, Keim V, Mossner J, Teich N, Sahin-Toth M (2008) Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis. Nat Genet 40:78–82

    PubMed  CAS  Google Scholar 

  • Sahin-Toth M, Toth M (2000) Gain-of-function mutations associated with hereditary pancreatitis enhance autoactivation of human cationic trypsinogen. Biochem Biophys Res Commun 278:286–289

    PubMed  CAS  Google Scholar 

  • Sarles H, Sarles JC, Camatte R, Muratore R, Gaini M, Guien C, Pastor J, Le Roy F (1965) Observations on 205 confirmed cases of acute pancreatitis, recurring pancreatitis, and chronic pancreatitis. Gut 6:545–559

    PubMed  CAS  Google Scholar 

  • Scheele GA, Fukuoka SI, Kern HF, Freedman SD (1996) Pancreatic dysfunction in cystic fibrosis occurs as a result of impairments in luminal pH, apical trafficking of zymogen granule membranes, and solubilization of secretory enzymes. Pancreas 12:1–9

    PubMed  CAS  Google Scholar 

  • Sherwood MW, Prior IA, Voronina SG, Barrow SL, Woodsmith JD, Gerasimenko OV, Petersen OH, Tepikin AV (2007) Activation of trypsinogen in large endocytic vacuoles of pancreatic acinar cells. Proc Natl Acad Sci USA 104:5674–5679

    PubMed  CAS  Google Scholar 

  • Simon P, Weiss FU, Sahin-Toth M, Parry M, Nayler O, Lenfers B, Schnekenburger J, Mayerle J, Domschke W, Lerch MM (2002) Hereditary pancreatitis caused by a novel PRSS1 mutation (Arg-122 –> Cys) that alters autoactivation and autodegradation of cationic trypsinogen. J Biol Chem 277:5404–5410

    PubMed  CAS  Google Scholar 

  • Singh M, LaSure MM, Bockman DE (1982) Pancreatic acinar cell function and morphology in rats chronically fed an ethanol diet. Gastroenterology 82:425–434

    PubMed  CAS  Google Scholar 

  • Suzuki A, Naruse S, Kitagawa M, Ishiguro H, Yoshikawa T, Ko SB, Yamamoto A, Hamada H, Hayakawa T (2001) 5-hydroxytryptamine strongly inhibits fluid secretion in guinea pig pancreatic duct cells. J Clin Invest 108:749–756

    PubMed  CAS  Google Scholar 

  • Szucs A, Demeter I, Burghardt B, Ovari G, Case RM, Steward MC, Varga G (2006) Vectorial bicarbonate transport by Capan-1 cells: a model for human pancreatic ductal secretion. Cell Physiol Biochem 18:253–264

    PubMed  CAS  Google Scholar 

  • Tahmasebi M, Puddefoot JR, Inwang ER, Vinson GP (1999) The tissue renin-angiotensin system in human pancreas. J Endocrinol 161:317–322

    PubMed  CAS  Google Scholar 

  • Thevenod F (2002) Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins. Am J Physiol Cell Physiol 283:C651–C672

    PubMed  CAS  Google Scholar 

  • Thevenod F, Kemmer TP, Christian AL, Schulz I (1989) Characterization of MgATP-driven H+ uptake into a microsomal vesicle fraction from rat pancreatic acinar cells. J Membr Biol 107:263–275

    PubMed  CAS  Google Scholar 

  • Thevenod F, Roussa E, Benos DJ, Fuller CM (2003) Relationship between a HCO3 –-permeable conductance and a CLCA protein from rat pancreatic zymogen granules. Biochem Biophys Res Commun 300:546–554

    PubMed  CAS  Google Scholar 

  • Thrower EC, Gorelick FS, Husain SZ (2010) Molecular and cellular mechanisms of pancreatic injury. Curr Opin Gastroenterol 26:484–489

    PubMed  CAS  Google Scholar 

  • Topazian M, Pandol S (2009) Acute pancreatitis. In: Yamada T (ed) Textbook of gastroenterology, vol 2. Wiley-Blackwell, Oxford, pp 1761–1811

    Google Scholar 

  • Toyama MT, Patel AG, Nguyen T, Ashley SW, Reber HA (1997) Effect of ethanol on pancreatic interstitial pH and blood flow in cats with chronic pancreatitis. Ann Surg 225:223–228

    PubMed  CAS  Google Scholar 

  • Venglovecz V, Rakonczay Z Jr, Ozsvari B, Takacs T, Lonovics J, Varro A, Gray MA, Argent BE, Hegyi P (2008) Effects of bile acids on pancreatic ductal bicarbonate secretion in guinea pig. Gut 57:1102–1112

    PubMed  CAS  Google Scholar 

  • Venglovecz V, Hegyi P, Rakonczay Z Jr, Tiszlavicz L, Nardi A, Grunnet M, Gray MA (2011a) Pathophysiological relevance of apical large-conductance Ca(2)+−activated potassium channels in pancreatic duct epithelial cells. Gut 60:361–369

    PubMed  CAS  Google Scholar 

  • Venglovecz V, Judák L, Rakonczay Z, Gray M, Hegyi P (2011b) Effects of ethanol and its non-oxidative metabolites on CFTR activity in guinea pig pancreatic duct cells. Gut 60:A363

    Google Scholar 

  • Venglovecz V, Rakonczay Z Jr, Hegyi P (2012) The effects of bile acids on pancreatic ductal cells. Pancreapedia 1–8

    Google Scholar 

  • Voronina S, Longbottom R, Sutton R, Petersen OH, Tepikin A (2002) Bile acids induce calcium signals in mouse pancreatic acinar cells: implications for bile-induced pancreatic pathology. J Physiol 540:49–55

    PubMed  CAS  Google Scholar 

  • Voronina SG, Barrow SL, Gerasimenko OV, Petersen OH, Tepikin AV (2004) Effects of secretagogues and bile acids on mitochondrial membrane potential of pancreatic acinar cells: comparison of different modes of evaluating DeltaPsim. J Biol Chem 279:27327–27338

    PubMed  CAS  Google Scholar 

  • Voronina SG, Barrow SL, Simpson AW, Gerasimenko OV, da Silvia Xavier G, Rutter GA, Petersen OH, Tepikin AV (2010) Dynamic changes in cytosolic and mitochondrial ATP levels in pancreatic acinar cells. Gastroenterology 138:1976–1987

    PubMed  CAS  Google Scholar 

  • Walters MN (1965) Goblet-cell metaplasia in ductules and acini of the exocrine pancreas. J Pathol Bacteriol 89:569–572

    PubMed  CAS  Google Scholar 

  • Wang Y, Soyombo AA, Shcheynikov N, Zeng W, Dorwart M, Marino CR, Thomas PJ, Muallem S (2006) Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO3 – secretion: relevance to cystic fibrosis. EMBO J 25:5049–5057

    PubMed  CAS  Google Scholar 

  • Wang Y, Sternfeld L, Yang F, Rodriguez JA, Ross C, Hayden MR, Carriere F, Liu G, Hofer W, Schulz I (2009) Enhanced susceptibility to pancreatitis in severe hypertriglyceridaemic lipoprotein lipase-deficient mice and agonist-like function of pancreatic lipase in pancreatic cells. Gut 58:422–430

    PubMed  CAS  Google Scholar 

  • Werner J, Laposata M, Fernandez-del Castillo C, Saghir M, Iozzo RV, Lewandrowski KB, Warshaw AL (1997) Pancreatic injury in rats induced by fatty acid ethyl ester, a nonoxidative metabolite of alcohol. Gastroenterology 113:286–294

    PubMed  CAS  Google Scholar 

  • Whitcomb DC, Lowe ME (2007) Human pancreatic digestive enzymes. Dig Dis Sci 52:1–17

    PubMed  CAS  Google Scholar 

  • Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK Jr, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD (1996) Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 14:141–145

    PubMed  CAS  Google Scholar 

  • Witt H, Luck W, Hennies HC, Classen M, Kage A, Lass U, Landt O, Becker M (2000) Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet 25:213–216

    PubMed  CAS  Google Scholar 

  • Wright AM, Gong X, Verdon B, Linsdell P, Mehta A, Riordan JR, Argent BE, Gray MA (2004) Novel regulation of cystic fibrosis transmembrane conductance regulator (CFTR) channel gating by external chloride. J Biol Chem 279:41658–41663

    PubMed  CAS  Google Scholar 

  • Yamamoto A, Ishiguro H, Ko SB, Suzuki A, Wang Y, Hamada H, Mizuno N, Kitagawa M, Hayakawa T, Naruse S (2003) Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells. J Physiol 551:917–926

    PubMed  CAS  Google Scholar 

  • Yang F, Wang Y, Sternfeld L, Rodriguez JA, Ross C, Hayden MR, Carriere F, Liu G, Schulz I (2009) The role of free fatty acids, pancreatic lipase and Ca+ signalling in injury of isolated acinar cells and pancreatitis model in lipoprotein lipase-deficient mice. Acta Physiol (Oxf) 195:13–28

    CAS  Google Scholar 

  • Yegutkin GG, Samburski SS, Jalkanen S, Novak I (2006) ATP-consuming and ATP-generating enzymes secreted by pancreas. J Biol Chem 281:29441–29447

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The research on pancreatic ducts was mostly supported by Hungarian National Development Agency grants (TÁMOP-4.2.2.A-11/1/KONV-2012-0035, TÁMOP-4.2.2-A-11/1/KONV-2012-0052 TÁMOP-4.2.2.A-11/1/KONV-2012-0073), the Hungarian Scientific Research Fund (OTKA NF105758, NF100677), and the Hungarian Academy of Sciences (BO 00174/10/5). Whereas, the experimental work on acinar cells was supported by Medical Research Council Programme Grants G0700167 and MR/J002771/1 as well as a Medical Research Council Professorship for OHP (G19/22/2). The authors declare that the experiments performed by them using the above-mentioned sources comply with the current laws of the country in which they were performed.

Author information

Authors and Affiliations

  1. First Department of Medicine, University of Szeged, Koranyi fsr. 8, SZEGED, H6720, Hungary

    Peter Hegyi

  2. MRC Group, School of Biosciences, Cardiff University, Sir Martin Evans Building, Wales, CF10 3AX, UK

    Ole H. Petersen

Authors
  1. Peter Hegyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ole H. Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Hegyi .

Editor information

Editors and Affiliations

  1. Dept. of Cell. and Molecular Medicine Lab. of Ion Channel Research, KU Leuven, Leuven, Belgium

    Bernd Nilius

  2. Deptartment of Neurobiology Biomedical Science Tower 3, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Susan G. Amara

  3. Walther-Straub-Institut für Pharmakologi, Ludwig-Maximilians-Universität München Medizinische Fakultät, München, Germany

    Thomas Gudermann

  4. MPI für Biophysikalische Chemie Abt. Neurobiologie, Göttingen, Germany

    Reinhard Jahn

  5. Zytopathologie, Universität Marburg Inst. Zytobiologie und, Marburg, Germany

    Roland Lill

  6. Abteilung II, Max-Planck-Institut für Herz- und Lungen, Bad Nauheim, Germany

    Stefan Offermanns

  7. Cardiff University School of Biosciences, Cardiff, United Kingdom

    Ole H. Petersen

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Hegyi, P., Petersen, O.H. (2013). The Exocrine Pancreas: The Acinar-Ductal Tango in Physiology and Pathophysiology. In: Nilius, B., et al. Reviews of Physiology, Biochemistry and Pharmacology, Vol. 165. Reviews of Physiology, Biochemistry and Pharmacology, vol 165. Springer, Cham. https://doi.org/10.1007/112_2013_14

Download citation

Publish with us

Policies and ethics

Search

Navigation